On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes
Identifieur interne : 003131 ( PascalFrancis/Curation ); précédent : 003130; suivant : 003132On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes
Auteurs : Ravikumar Rajamanonmani [Singapour] ; Celine Nkenfou [Singapour] ; Paula Clancy [Australie] ; YIN HOE YAU [Singapour] ; Susana Geifman Shochat [Singapour] ; Soila Sukupolvi-Petty [États-Unis] ; Wouter Schul [Singapour] ; Michael S. Diamond [États-Unis] ; Subhash G. Vasudevan [Singapour, Australie] ; Julien Lescar [Singapour, France]Source :
- Journal of general virology [ 0022-1317 ] ; 2009.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F1 2 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F1 2 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F1 2 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.
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<front><div type="abstract" xml:lang="en">The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F1 2 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F1 2 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F1 2 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.</div>
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<fC03 i1="04" i2="X" l="FRE"><s0>Anticorps monoclonal</s0>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Monoclonal antibody</s0>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Anticuerpo monoclonal</s0>
<s5>06</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Sérotype</s0>
<s5>07</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Serotype</s0>
<s5>07</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Serotipo</s0>
<s5>07</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Microbiologie</s0>
<s5>08</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Microbiology</s0>
<s5>08</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Microbiología</s0>
<s5>08</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Virus groupe dengue</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Dengue group virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Dengue group virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Flavivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Flavivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Flavivirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Flaviviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Flaviviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Flaviviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fN21><s1>117</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>
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